Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma.

Abstract

Peripheral T-cell lymphoma (PTCL) encompasses a heterogeneous group of neoplasms with generally poor clinical outcome. Currently 50% of PTCL cases are not classifiable: PTCL-not otherwise specified (NOS). Gene-expression profiles on 372 PTCL cases were analyzed and robust molecular classifiers and oncogenic pathways that reflect the pathobiology of tumor cells and their microenvironment were identified for major PTCL-entities, including 114 angioimmunoblastic T-cell lymphoma (AITL), 31 anaplastic lymphoma kinase (ALK)-positive and 48 ALK-negative anaplastic large cell lymphoma, 14 adult T-cell leukemia/lymphoma and 44 extranodal NK/T-cell lymphoma that were further separated into NK-cell and gdT-cell lymphomas. Thirty-seven percent of morphologically diagnosed PTCL-NOS cases were reclassified into other specific subtypes by molecular signatures. Reexamination, immunohistochemistry, and IDH2 mutation analysis in reclassified cases supported the validity of the reclassification. Two major molecular subgroups can be identified in the remaining PTCL-NOS cases characterized by high expression of either GATA3 (33%; 40/121) or TBX21 (49%; 59/121). The GATA3 subgroup was significantly associated with poor overall survival (P = .01). High expression of cytotoxic gene-signature within the TBX21 subgroup also showed poor clinical outcome (P = .05). In AITL, high expression of several signatures associated with the tumor microenvironment was significantly associated with outcome. A combined prognostic score was predictive of survival in an independent cohort (P = .004).

• Authors: Javeed Iqbal, George Wright, Chao Wang, Andreas Rosenwald, Randy D Gascoyne, Dennis D Weisenburger, Timothy C Greiner, Lynette Smith, Shuangping Guo, Ryan A Wilcox, Bin Tean Teh, Soon Thye Lim, Soon Yong Tan, Lisa M Rimsza, Elaine S Jaffe, Elias Campo, Antonio Martinez, Jan Delabie, Rita M Braziel, James R Cook, Raymond R Tubbs, German Ott, Eva Geissinger, Philippe Gaulard, Pier Paolo Piccaluga, Stefano A Pileri, Wing Y Au, Shigeo Nakamura, Masao Seto, Francoise Berger, Laurence de Leval, Joseph M Connors, James Armitage, Julie Vose, Wing C Chan, Louis M Staudt, Lymphoma Leukemia Molecular Profiling Project and the International Peripheral T-cell Lymphoma Project
• Journal: Blood (Blood) Vol. 123 Issue 19 Pg. 2915-23 (May 08 2014) ISSN: 1528-0020 [Electronic] United States
• PMID: 24632715 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Biomarkers, Tumor

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (genetics, metabolism)
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Lymphoma, T-Cell, Peripheral (classification, diagnosis, genetics)
• Male
• Middle Aged
• Oligonucleotide Array Sequence Analysis
• Prognosis
• Survival Analysis
• Young Adult